BACKGROUND: The pathophysiology of Hirschsprung's disease (HSCR) is not fully understood. A significant proportion of patients have persisting bowel symptoms such as constipation, soiling, and enterocolitis despite correctly performed operations. Animal data suggest that stretch-activated 2-pore domain K+ channels play a critical role in the maintenance of intestinal barrier integrity. METHODS: We investigated TREK-1 protein expression in ganglionic and aganglionic regions of HSCR patients (n = 10) vs. normal control colon (n = 10). Protein distribution was assessed by using immunofluorescence and confocal microscopy. Gene and protein expression were quantified using quantitative real-time polymerase chain reaction, western blot analysis, and densitometry. RESULTS: Confocal microscopy of the normal colon revealed strong TREK-1 channel expression in the epithelium. TREK-1-positive cells were decreased in aganglionic and ganglionic bowel compared to controls. TREK-1 gene expression levels were significantly decreased in aganglionic and ganglionic bowel compared to controls (P < 0.05). Western blotting revealed decreased TREK-1 protein expression in aganglionic and ganglionic bowel compared to controls. CONCLUSION: We demonstrate, for the first time, the expression and distribution of TREK-1 channels in the human colon. The decreased TREK-1 expression in the aganglionic and ganglionic bowel observed in HSCR may alter intestinal epithelial barrier function leading to the development of enterocolitis.
BACKGROUND: The pathophysiology of Hirschsprung's disease (HSCR) is not fully understood. A significant proportion of patients have persisting bowel symptoms such as constipation, soiling, and enterocolitis despite correctly performed operations. Animal data suggest that stretch-activated 2-pore domain K+ channels play a critical role in the maintenance of intestinal barrier integrity. METHODS: We investigated TREK-1 protein expression in ganglionic and aganglionic regions of HSCR patients (n = 10) vs. normal control colon (n = 10). Protein distribution was assessed by using immunofluorescence and confocal microscopy. Gene and protein expression were quantified using quantitative real-time polymerase chain reaction, western blot analysis, and densitometry. RESULTS: Confocal microscopy of the normal colon revealed strong TREK-1 channel expression in the epithelium. TREK-1-positive cells were decreased in aganglionic and ganglionic bowel compared to controls. TREK-1 gene expression levels were significantly decreased in aganglionic and ganglionic bowel compared to controls (P < 0.05). Western blotting revealed decreased TREK-1 protein expression in aganglionic and ganglionic bowel compared to controls. CONCLUSION: We demonstrate, for the first time, the expression and distribution of TREK-1 channels in the human colon. The decreased TREK-1 expression in the aganglionic and ganglionic bowel observed in HSCR may alter intestinal epithelial barrier function leading to the development of enterocolitis.
Authors: Susanne A Snoek; Marleen I Verstege; Guy E Boeckxstaens; René M van den Wijngaard; Wouter J de Jonge Journal: Expert Rev Gastroenterol Hepatol Date: 2010-10 Impact factor: 3.869
Authors: Malla I Neuvonen; Kristiina Kyrklund; Harry G Lindahl; Antti I Koivusalo; Risto J Rintala; Mikko P Pakarinen Journal: J Pediatr Surg Date: 2015-02-14 Impact factor: 2.545
Authors: Tatiana Zyrianova; Benjamin Lopez; Riccardo Olcese; John Belperio; Christopher M Waters; Leanne Wong; Victoria Nguyen; Sriharsha Talapaneni; Andreas Schwingshackl Journal: Sci Rep Date: 2020-12-15 Impact factor: 4.379